An optically active sulfoxide derivative having an antiulcer activity can be obtained by asymmetric oxidization of a prochiral sulfide derivative. Generally, the above-mentioned reaction produces sulfone, which is an excess reaction product. As a result, the obtained sulfoxide derivative comprises, as analogous substances, unreacted sulfide derivatives and sulfone derivatives as excess reaction products.
As a production method for obtaining an optically active sulfoxide derivative, for example, WO 96/02535 (Japanese Patent Application under PCT laid-open under kohyo No. Hei 10-504290) discloses a method comprising reacting a sulfide derivative and an oxidizing agent in an organic solvent in the presence of a chiral titanium complex and a base to give an optically active sulfoxide compound.
For example, in Example 22 of this publication, it is described that a mixture, which was obtained by adding water (3.6 mmol), (+)-diethyl L-tartrate (15.0 mmol) and titanium(IV) isopropoxide (6.0 mmol) to a solution of 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]thio]-1H-benzimidazole (6.0 mmol) in toluene, stirring the resulting mixture at 50° C. for 60 min, cooling the reaction mixture to room temperature, adding N,N-diisopropylethylamine (6.0 mmol) and cumene hydroperoxide (6.0 mmol) and stirring the mixture at room temperature for 16 hr, consisted of 13% of sulfide, 8% of sulfone and 76% of sulfoxide as determined by achiral HPLC, that post-treatments of purification by flash chromatography and the like gave (+)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole (0.85 g) showing 46%ee enantiomer excess, and that, by further purification, 0.31 g (14%) of the objective substance having an optical purity of 99.6%ee was ultimately obtained as an oily substance.
JP-A-2000-16992 discloses a method for obtaining a sulfoxide compound, which comprises oxidizing a particular thioether compound with N-halosuccinimide, 1,3-dihalo-5,5-dimethylhydantoin or dichlorocyanuric acid salt in the presence of a base. It further teaches that, depending on the reaction conditions, the reaction may not terminate with the production of sulfoxide and a side reaction may occur, wherein a part of the resulting sulfoxide is further oxidized into sulfone, and production of sulfone decreases the yield of the objective sulfoxide, and that because the physical and chemical properties of the both are extremely similar, their separation and purification is difficult.
Conventional production methods are associated with the problems that a sulfone form, which is difficult to remove, is produced, that the objective optically active sulfoxide form has a low optical purity (enantiomer excess), thus essentially requiring purification by column chromatography and the like, and that the yield is low. In view of the above, a production method of an optically active sulfoxide derivative having an antiulcer activity is desired, which is industrially advantageous from the aspects of amount of analogous substances present therein, optical purity, yield, productivity and economic aspect.